Effects of Nonsteroidal Anti-inflammatory Drugs on Transforming Growth Factor-β Expression and Bioactivity in Rat Osteoblast-enriched Cultures

非類固醇消炎藥物對大鼠成骨細胞之乙型轉型生長因子之表現與活性之影響

張瑞根(Je-Ken Chang) ； 莊麗月(Lea-Yea Chuang) ； 何美泠(Mei-Ling Ho) ； 王國照(Gwo-Jaw Wang)

《The Kaohsiung Journal of Medical Sciences》 19卷6期 (2003/06) Pp. 278-288

摘要

研究報告曾指出類固醇消炎藥(NSAIDs)會抑制正常骨復骨之骨重塑作用。我們過去的研究結果發現ketorolac和indomethacin對培養乙型轉型生長因子(TGF-β)會促進成骨細胞之增殖，抑制分化及預防凋亡之作用。研究報告曾指出乙型轉型生長因子(TGF-β)會促進成骨細胞之增殖抑制分化及預防凋亡作用。因此，我們假設NSAIDs對成骨細功能之影響其中之一路徑，可能是抑制TGF-β之表現或其生物活性而造成。為測試此一假設，我們測定ketorolac 與indomethacin對取自大鼠頭顱骨之成骨細胞的TGF-β1 mRNA與蛋白質之表現以及TGF-β之表現與活性之影響。我們並且測定前列腺素 E1 (PGE1) 和(PGE2)對TGF-β之表現與活性之影響，以便瞭解更多有關PGs在成骨細胞所扮演的角色。同時我們也評估NSAIDs的作用是否透過PG的途徑而產生。結果顯示處理PGEs和理論之治療濃度之ketorolac和indomethacin24小時後並無顯著影響TGF-β之轉錄、轉譯以及轉譯之後的功能。這些結果建議NSAIDs對成骨細胞功能之影響不是透過影響TGF-β的作用使然。

關鍵字

非類固醇消炎藥物 ； 前列腺素 ； 成骨細胞 ； 乙型轉型生長因子

並列摘要

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been reported to suppress bone remodeling in ormal and repaired bones. Our previous results indicated that ketorolac and indomethacin suppressed proliferation, stimulated early differentiation, and induced apoptosis in cultured osteoblasts. Transforming growth factor-β (TGF-β) has been reported to enhance proliferation, suppress differentiation, and prevent apoptosis in osteoblasts. We proposed that one pathway of NSAID effects on osteoblast function might be through inhibition of the expression and / or bioactivity of TGF-β in osteoblasts. We tested the effects of ketorolac and indomethacin on the expression of TGF-βl mRNA and protein and the bioactivity of TGF-β in osteoblast-enriched cultures derived from fetal calvaria. The effects of prostaglandin E1 (PGE1) and PGE2 on TGF-β expression and bioactivity were also examined in order to understand more about the role of prostaglandins in osteoblast function. Simultaneously, we estimated whether these NSAID effects on osteoblasts were prostaglandin-related. The results showed that 24-hour treatments with both PGEs and theoretic therapeutic concentrations of ketorolac and indomethacin had no significant effects on the levels of either transcription or translation of TGF-β or the post-translational function of TGF-β in osteoblasts. These results suggest that NSAIDs do not affect osteoblast function through changes in TGF-β action in osteoblasts.

並列關鍵字

nonsteroidal anti-inflammatory drugs ； prostaglandins ； osteoblasts ； transforming growth factor-β